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  • Cyclic Hypobaric Hypoxia Improves Markers of Glucose Metabolism in Middle-Aged Men HIGH ALTITUDE MEDICINE & BIOLOGY Marquez, J. L., Rubinstein, S., Fattor, J. A., Shah, O., Hoffman, A. R., Friedlander, A. L. 2013; 14 (3): 263-272


    Chronic hypoxia increases dependence on glucose in men and increases insulin sensitivity in men and women. Cyclic Variations in Altitude Conditioning (CVAC) is a novel technology that provides exposure to rapidly fluctuating cyclic hypobaric hypoxia (CHH).To test the hypothesis that markers of glucose metabolism would change with CVAC CHH, two groups of middle-aged men were exposed to 10 weeks (40 min/day, 3 day/week) of either CHH or sham (SH) sessions.CHH subjects (age: 48 ± 6, weight: 86 ± 12 kg, BMI: 27.1 ± 3, n=11) experienced cyclic pressures simulating altitudes ranging from sea level to 3048 m (week 1) and progressing to 6096 m (by week 5 through week 10). SH subjects (age: 50 ± 4, weight: 89 ± 15 kg, BMI: 27.5 ± 3, n=10) were exposed to slowly-fluctuating pressures up to 607 m (all subjects blinded to elevation). Physical function and blood markers of glucose metabolism were measured at baseline, 3, 6, and 10 weeks.Two CHH subjects were dropped from analysis for failure to progress past 3048 m (CHH: n=9). Weight and physical activity remained stable for both groups. There was a group-by-time interaction in fasting glucose (CHH: 96 ± 9 to 91 ± 7 mg/dL, SH: 94 ± 7 to 97 ± 9 mg/dL, p<0.05). Reduction in plasma glucose response to oral glucose tolerance test [area under the curve] was greater in CHH compared to SH after 10 weeks of exposure (p<0.03). Neither group experienced changes in fasting insulin, insulin response during the OGTT, or changes in a timed walk test.Ten weeks of CVAC CHH exposure improves markers of glucose metabolism in middle-aged men at risk for metabolic syndrome.

    View details for DOI 10.1089/ham.2012.1057

    View details for Web of Science ID 000324834700019

    View details for PubMedID 24028640

  • Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY Kressler, J., Stoutenberg, M., Roos, B. A., Friedlander, A. L., Perry, A. C., Signorile, J. F., Jacobs, K. A. 2011; 111 (12): 3031-3040


    Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥ 4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO(2)), peak exercise capacity (W (peak)), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% F(I)O(2)) and high (HA; ~3,900 m, 12.8% F(I)O(2)) altitudes. Eleven men and ten women completed two HA W (peak) trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W (peak) + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO(2) values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W (peak) at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.

    View details for DOI 10.1007/s00421-011-1930-3

    View details for Web of Science ID 000297174800015

    View details for PubMedID 21451938

  • Sildenafil Has Little Influence on Cardiovascular Hemodynamics or 6-km Time Trial Performance in Trained Men and Women at Simulated High Altitude HIGH ALTITUDE MEDICINE & BIOLOGY Jacobs, K. A., Kressler, J., Stoutenberg, M., Roos, B. A., Friedlander, A. L. 2011; 12 (3): 215-222


    Sildenafil improves maximal exercise capacity at high altitudes (∼4350-5800 m) by reducing pulmonary arterial pressure and enhancing oxygen delivery, but the effects on exercise performance at less severe altitudes are less clear.To determine the effects of sildenafil on cardiovascular hemodynamics (heart rate, stroke volume, and cardiac output), arterial oxygen saturation (SaO2), and 6-km time-trial performance of endurance-trained men and women at a simulated altitude of ∼3900 m.Twenty men and 15 women, endurance-trained, completed one experimental exercise trial (30 min at 55% of altitude-specific capacity +6-km time trial) at sea level (SL) and two trials at simulated high altitude (HA) while breathing hypoxic gas (12.8% FIo2) after ingestion of either placebo or 50 mg sildenafil in double-blind, randomized, and counterbalanced fashion.Maximal exercise capacity and SaO2 were significantly reduced at HA compared to SL (18%-23%), but sildenafil did not significantly improve cardiovascular hemodynamics or time-trial performance in either men or women compared to placebo and only improved SaO2 in women (4%). One male subject (5% of male subjects, 2.8% of all subjects) exhibited a meaningful 36-s improvement in time-trial performance with sildenafil compared to placebo.In this group of endurance trained men and women, sildenafil had very little influence on cardiovascular hemodynamics, SaO2, and 6-km time-trial performance at a simulated altitude of ∼3900 m. It appears that a very small percentage of endurance-trained men and women derive meaningful improvements in aerobic performance from sildenafil at a simulated altitude of ∼3900 m.

    View details for DOI 10.1089/ham.2011.0011

    View details for Web of Science ID 000295406200004

    View details for PubMedID 21962064

  • Evaluating Technology that Makes Physical Games for Children more Engaging Peer, F., Mazalek, A., Mueller, F., Friedlander, A., ACM ASSOC COMPUTING MACHINERY. 2011: 193–96
  • Sildenafil Does Not Improve Peak Exercise Capacity During Acute Hypoxia In Trained Men Or Women. Kressler, J., Stoutenberg, M., Roos, B., Friedlander, A. L., Perry, A. C., Signorile, J., Viskochil, R., Jacobs, K. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: 141
  • Men And Women Exhibit Similar Declines In Peak Exercise Capacity And Performance At Simulated Altitudes. Viskochil, R., Kressler, J., Stoutenberg, M., Roos, B., Friedlander, A. L., Perry, A. C., Signorile, J., Jacobs, K. LIPPINCOTT WILLIAMS & WILKINS. 2010: 470
  • Sildenafil Does Not Improve Performance At Simulated High Or Moderate Altitudes In Men Or Women. Stoutenberg, M., Kressler, J., Roos, B., Friedlander, A. L., Viskochil, R., Signorile, J. F., Jacobs, K. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: 470
  • MAKING MOLEHILLS OUT OF MOUNTAINS: Maintaining High Performance at Altitude ACSMS HEALTH & FITNESS JOURNAL Friedlander, A. L., Braun, B., Marquez, J. 2008; 12 (6): 15-21
  • Systematic review: The effects of growth hormone on athletic performance ANNALS OF INTERNAL MEDICINE Liu, H., Bravata, D. M., Olkin, I., Friedlander, A., Liu, V., Roberts, B., Bendavid, E., Saynina, O., Salpeter, S. R., Garber, A. M., Hoffman, A. R. 2008; 148 (10): 747-U59


    Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood.To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals.MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007.Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age.2 authors independently reviewed articles and abstracted data.44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone.Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens.Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.

    View details for Web of Science ID 000256372200004

    View details for PubMedID 18347346

  • Effects of growth hormone and pioglitazone in viscerally obese adults with impaired glucose tolerance: A factorial clinical trial PLOS CLINICAL TRIALS Attallah, H., Friedlander, A. L., Nino-Murcia, M., Hoffman, A. R. 2007; 2 (5)


    Recombinant human growth hormone (GH) and pioglitazone (PIO) in abdominally obese adults with impaired glucose tolerance were evaluated under the hypothesis that the combination attenuates GH-induced increases in glucose concentrations, reduces visceral adipose tissue (VAT), and improves insulin sensitivity over time.Randomized, double-blind, placebo-controlled, 2 x 2 factorial design.Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States.62 abdominally obese adults aged 40-75 with impaired glucose tolerance.GH (8 microg/kg/d, or placebo) and pioglitazone (30 mg/d, or placebo) for 40 wk.Baseline and after 40 wk of treatment, VAT content was quantified by CT scan, glucose tolerance was assessed using a 75-g oral glucose tolerance test, and insulin sensitivity was measured using steady-state plasma glucose levels obtained during insulin suppression test.BASELINE: body mass index (BMI), plasma glucose, and visceral fat content were similar. 40 wk: visceral fat area declined 23.9 +/- 7.4 cm(2) in GH group, mean difference from placebo: -28.1 cm(2) (95% CI -49.9 to -6.3 cm(2); p = 0.02). Insulin resistance declined 52 +/- 11.8 mg/dl with PIO, mean difference from placebo of -58.8 mg/dl (95% CI -99.7 to -18.0 mg/dl; p = 0.01). VAT and SSPG declined with GH and PIO combined, mean differences from placebo of -31.4 cm(2) (95% CI -56.5 cm(2) to -6.3 cm(2); p = 0.02) and -55.3 mg/dl (95% CI -103.9 to -6.7 mg/dl; p = 0.02), respectively. Fasting plasma glucose increased transiently in GH group. No significant changes in BMI were observed.Addition of PIO to GH attenuated the short-term diabetogenic effect of GH; the drug combination reduced VAT and insulin resistance over time. GH plus PIO may have added benefit on body composition and insulin sensitivity in the metabolic syndrome.

    View details for DOI 10.1371/journal.pctr.0020021

    View details for Web of Science ID 000246737100002

    View details for PubMedID 17479164

    View details for PubMedCentralID PMC1865086

  • Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women BRITISH JOURNAL OF NUTRITION Holloway, L., Moynihan, S., Abrams, S. A., Kent, K., Hsu, A. R., Friedlander, A. L. 2007; 97 (2): 365-372


    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

    View details for DOI 10.1017/S000711450733674X

    View details for Web of Science ID 000244647400020

    View details for PubMedID 17298707

  • Visceral obesity, impaired glucose tolerance, metabolic syndrome, and growth hormone therapy 19th Annual National Cooperative Growth Study/1st Annual National Cooperative Metabolic Study Investigator Meeting Attallah, H., Friedlander, A. L., Hoffman, A. R. CHURCHILL LIVINGSTONE. 2006: S62–S67


    Overweight adults with impaired glucose tolerance have a 5-10% risk of developing diabetes per year, and insulin resistance is an important cause of progression to diabetes in these individuals. Weight loss has been shown to improve insulin sensitivity and prevent or delay progression to diabetes. According to recent studies, the improvement in insulin sensitivity that occurs with weight loss is closely linked to the reduction of visceral adipose tissue (VAT), the collection of intra-abdominal adipose depots that includes omental and intrahepatic fat. After controlling for BMI, whole body fat, and subcutaneous fat, only VAT is an independent predictor of endogenous insulin sensitivity and glucose tolerance before or after weight loss. This, in turn, suggests that reducing VAT is crucial to improving insulin sensitivity and preventing diabetes in high-risk individuals. Recombinant human growth hormone (GH) is a lipolytic drug that reduces total body, abdominal, and visceral fat in growth hormone-deficient (GHD) adults. Several studies have reported substantial reductions in VAT following GH treatment in this population. Like GHD adults, abdominally obese individuals have increased VAT, insulin resistance, and growth hormone levels that are below normal during continuous 24-h monitoring. These similarities have prompted a number of recent investigations in abdominally obese adults that reported significant reductions in truncal and visceral fat and an improvement in insulin sensitivity following prolonged GH administration. However, other studies have shown that insulin resistance and glucose concentrations transiently worsen during the first few weeks of GH treatment and that these deleterious effects can persist even after VAT reduction has occurred. Prior studies involving GH treatment were generally limited to adults who were normoglycemic at baseline. Less is known about the effects of GH in adults with impaired glucose tolerance or diabetes. The effects of GH used in conjunction with insulin sensitizers on glycemic control and VAT in patients with impaired glucose tolerance will be reviewed.

    View details for DOI 10.1016/j.ghir.2006.03.004

    View details for Web of Science ID 000239821100011

    View details for PubMedID 16624603

  • Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM Barnholt, K. E., Hoffman, A. R., Rock, P. B., Muza, S. R., Fulco, C. S., Braun, B., Holloway, L., Mazzeo, R. S., Cymerman, A., Friedlander, A. L. 2006; 290 (6): E1078-E1088


    High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

    View details for DOI 10.1152/ajpendo.00449.2005

    View details for Web of Science ID 000237803300003

    View details for PubMedID 16380390

  • Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia JOURNAL OF APPLIED PHYSIOLOGY Hsu, A. R., Barnholt, K. E., Grundmann, N. K., Lin, J. H., McCallum, S. W., Friedlander, A. L. 2006; 100 (6): 2031-2040


    Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.

    View details for DOI 10.1152/japplphysiol.00806.2005

    View details for Web of Science ID 000237896100037

    View details for PubMedID 16455814

  • Sildenafil Improves Cardiac Output and Exercise Performance During Acute Hypoxia Friedlander, A. L., Hsu, A. R., Lin, J. H., Branholt, K. E., Grundmann, N. K., McCallum, S. W. LIPPINCOTT WILLIAMS & WILKINS. 2006: 72
  • Cytokine response at high altitude: Effects of exercise and antioxidants at 4300 m MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Hagobian, T. A., Jacobs, K. A., Subudhi, A. W., Fattor, J. A., Rock, P. B., Muza, S. R., Fulc, C. S., Braun, B., Grediagin, A., Mazzeo, R. S., Cymerman, A., Friedlander, A. L. 2006; 38 (2): 276-285
  • Three weeks of caloric restriction alters protein metabolism in normal-weight, young men AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM Friedlander, A. L., Braun, B., Pollack, M., Macdonald, J. R., Fulco, C. S., Muza, S. R., Rock, P. B., Henderson, G. C., Horning, M. A., Brooks, G. A., Hoffman, A. R., Cymerman, A. 2005; 289 (3): E446-E455


    The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3, mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 and oxidation (R(ox); approximately 19 did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.

    View details for DOI 10.1152/ajpendo.00001.2005

    View details for Web of Science ID 000231394900013

    View details for PubMedID 15870104

  • Antioxidant supplementation does not attenuate oxidative stress at high altitude AVIATION SPACE AND ENVIRONMENTAL MEDICINE Subudhi, A. W., Jacobs, K. A., Hagobian, T. A., Fattor, J. A., Fulco, C. S., Muza, S. R., Rock, P. B., Hoffman, A. R., Cymerman, A., Friedlander, A. L. 2004; 75 (10): 881-888


    Hypobaric hypoxia and heightened metabolic rate increase free radical production.We tested the hypothesis that antioxidant supplementation would reduce oxidative stress associated with increased energy expenditure (negative energy balance) at high altitude (HA 4300 m).For 12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing included fasting blood and 24-h urine samples to assess antioxidant status [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary 8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak) oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress (plasma LPO, whole blood reduced and oxidized glutathione, glutathione peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned to either a placebo or antioxidant supplement group for a double-blinded trial. Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500 mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy intake and expenditure were adjusted to achieve a caloric deficit of approximately 1400 kcal. Fasting blood and 24-h urine samples were collected throughout HA and the OSI test was repeated on HA day 1 and day 13.Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased over HA with no effect of supplementation. Prolonged submaximal exercise was not associated with increased concentrations of oxidative stress markers at SL or HA.Antioxidant supplementation did not significantly affect markers of oxidative stress associated with increased energy expenditure at HA.

    View details for Web of Science ID 000224182100008

    View details for PubMedID 15497369

  • Foot cooling reduces exercise-induced hyperthermia in men with spinal cord injury MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Hagobian, T. A., Jacobs, K. A., Kiratli, B. J., Friedlander, A. L. 2004; 36 (3): 411-417


    The number of individuals with spinal cord injury (SCI) participating in sports at recreational and elite levels is on the rise. However, loss of autonomic nervous system function below the lesion can compromise thermoregulatory capacity and increase the risk of heat stress relative to able-bodied (AB) individuals.To test the hypotheses that exercise in a heated environment would increase tympanic temperature (TTY) more in individuals with SCI than AB individuals, and that foot cooling using a new device would attenuate the rise in TTY during exercise in both groups.Six subjects with SCI (lesions C5-T5) and six AB controls were tested in a heated environment (means +/- SEM, temperature = 31.8 +/- 0.2 degrees C, humidity = 26 +/- 1%) for 45 min at 66% +/- 5 of arm cranking VO2peak and 30 min of recovery on two separate occasions with foot cooling (FC) or no foot cooling (NC) in randomized order.During exercise and recovery in both trials, SCI TTY was elevated above baseline (P < 0.001) but more so in the NC versus FC trial (1.6 +/- 0.2 degrees C vs 1.0 +/- 0.2 degrees C, respectively, P < 0.005). Within the AB group, TTY was elevated above baseline for both trials (P < 0.001) with peak increases of 0.5 +/- 0.2 degrees C and 0.3 +/- 0.2 degrees C for NC and FC, respectively. TTY, face, and back temperature were higher in both SCI trials compared with AB trials (P < 0.05). Heart rate during exercise and recovery was lower in the SCI FC versus SCI NC (P < 0.05).These results suggest that extraction of heat through the foot may provide an effective way to manipulate tympanic temperature in individuals with SCI, especially during exercise in the heat.

    View details for DOI 10.1249/01.MSS.0000117133.75146.66

    View details for Web of Science ID 000220131800009

    View details for PubMedID 15076782

  • Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women METABOLISM-CLINICAL AND EXPERIMENTAL Braun, B., Friedlander, A. L., Pollack, M., Butterfield, G. E., Marcus, R., Hoffman, A. R. 2003; 52 (9): 1182-1190


    Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.

    View details for DOI 10.1016/S0026-0495(03)00166-5

    View details for Web of Science ID 000185365600015

    View details for PubMedID 14506625

  • Energy intake deficit and physical performance at altitude AVIATION SPACE AND ENVIRONMENTAL MEDICINE Fulco, C. S., Friedlander, A. L., Muza, S. R., Rock, P. B., Robinson, S., Lammi, E., Baker-Fulco, C. J., Lewis, S. F., Cymerman, A. 2002; 73 (8): 758-765


    Physical performance of sea-level (SL) residents acutely exposed to altitude (ALT) is diminished and may improve somewhat with ALT acclimatization.A large reduction in lean body mass (LBM), due to severe energy intake deficit during the first 21 d of ALT (4300 m) acclimatization, will adversely affect performance.At ALT, 10 men received a deficit (DEF) of 1500 kcal x d(-1) below body weight (BW) maintenance requirements and 7 men received adequate (ADQ) kcal x d(-1) to maintain BW. Performance was assessed by: 1) maximal oxygen uptake (VO2max); 2) time to complete 50 cycles of a lift and carry task (L+C); 3) number of one-arm elbow flexions (10% BW at 22 flexions x min(-1); and 4) adductor pollicis (AP) muscle strength and endurance time (repeated 5-s static contractions at 50% of maximal force followed by 5-s rest, to exhaustion). Performance and body composition (using BW and circumference measures) were determined at SL and at ALT on days 2 through 21.At SL, there were no between-group differences (p > 0.05) for any of the performance measures. From SL to day 21 at ALT, BW and LBM declined by 6.6 +/- 3 kg and 4.6 kg, respectively, for the DEF group (both p < 0.01), but did not change (both p > 0.05) for the ADQ group. Performance changes from day 2 or 3 to day 20 or 21 at ALT were as follows (values are means +/- SD): VO2max (ml x min(-1)): DEF = +97 +/- 237, ADQ = +159 +/- 156; L + C (s): DEF = -62 +/- 35*, ADQ = -35 +/- 20* (*p < 0.05; improved from day 3); arm flex (reps): DEF = -2 +/- 7, ADQ = +2 +/- 8; AP endurance (min): DEF = +1.4 +/- 2, ADQ = + 1.9 +/- 2; AP strength (kg): DEF = -0.7 +/- 4, ADQ = -1.2 +/- 2. There were no differences in performance between groups.A significant BW and LBM loss due to underfeeding during the first 21 d of ALT acclimatization does not impair physical performance at ALT.

    View details for Web of Science ID 000177238700004

    View details for PubMedID 12182215

  • One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Friedlander, A. L., Butterfield, E., Moynihan, S., Grillo, J., Pollack, M., Holloway, L., Friedman, L., Yesavage, J., Matthias, D. F., Lee, S., Marcus, R., Hoffman, A. R. 2001; 86 (4): 1496-1503


    The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

    View details for Web of Science ID 000168243000010

    View details for PubMedID 11297574

  • Endurance training increases fatty acid turnover, but not fat oxidation, in young men JOURNAL OF APPLIED PHYSIOLOGY Friedlander, A. L., Casazza, G. A., Horning, M. A., Usaj, A., Brooks, G. A. 1999; 86 (6): 2097–2105


    We examined the effects of exercise intensity and a 10-wk cycle ergometer training program [5 days/wk, 1 h, 75% peak oxygen consumption (VO2 peak)] on plasma free fatty acid (FFA) flux, total fat oxidation, and whole body lipolysis in healthy male subjects (n = 10; age = 25.6 +/- 1.0 yr). Two pretraining trials (45 and 65% of VO2 peak) and two posttraining trials (same absolute workload, 65% of old VO2 peak; and same relative workload, 65% of new VO2 peak) were performed by using an infusion of [1-13C]palmitate and [1,1,2,3, 3-2H]glycerol. An additional nine subjects (age 25.4 +/- 0.8 yr) were treated similarly but were infused with [1,1,2,3,3-2H]glycerol and not [1-13C]palmitate. Subjects were studied postabsorptive for 90 min of rest and 1 h of cycling exercise. After training, subjects increased VO2 peak by 9.4 +/- 1.4%. Pretraining, plasma FFA kinetics were inversely related to exercise intensity with rates of appearance (Ra) and disappearance (Rd) being significantly higher at 45 than at 65% VO2 peak (Ra: 8.14 +/- 1.28 vs. 6.64 +/- 0.46, Rd: 8. 03 +/- 1.28 vs. 6.42 +/- 0.41 mol. kg-1. min-1) (P

    View details for Web of Science ID 000080781400050

    View details for PubMedID 10368378

  • Effects of exercise intensity and training on lipid metabolism in young women. American journal of physiology. Endocrinology and metabolism Friedlander, A. L., Casazza, G. A., Horning, M. A., Buddinger, T. F., Brooks, G. A. 1998; 275 (5): E853–E863


    We examined the effects of exercise intensity and training [12 wk, 5 days/wk, 1 h, 75% peak oxygen consumption (V˙o 2 peak)] on lipolysis and plasma free fatty acid (FFA) flux in women ( n = 8; 24.3 ± 1.6 yr). Two pretraining trials (45 and 65% ofV˙o 2 peak) and two posttraining trials [same absolute workload (65% of oldV˙o 2 peak; ABT) and same relative workload (65% of newV˙o 2 peak; RLT)] were performed using infusions of [1,1,2,3,3-2H]glycerol and [1-13C]palmitate. Pretraining rates of FFA appearance (Ra), disappearance (Rd), and oxidation (Rox p) were similar between the 65% (6.8 ± 0.6, 6.2 ± 0.7, 3.1 ± 0.3 mumol kg-1 min-1, respectively) and the 45% ofV˙o 2 peaktrials. At ABT and RLT training increased FFA Ra to 8.4 ± 1.0 and 9.7 ± 1.1 mumol kg-1 min-1, Rd to 8.3 ± 1.0 and 9.5 ± 1.1 mumol kg-1 min-1, and Rox p to 4.8 ± 0.4 and 6.7 ± 0.7 mumol kg-1 min-1, respectively ( P ≤ 0.05). Total FFA oxidation from respiratory exchange ratio was also elevated after training at ABT and RLT, with all of the increase attributed to plasma FFA sources. Pretraining, glycerol Ra was higher during exercise at 65 than 45% of V˙o 2 peak(6.9 ± 0.9 vs. 4.7 ± 0.6 mumol kg-1 min-1) but was not changed by training. In young women 1) plasma FFA kinetics and oxidation are not linearly related to exercise intensity before training, 2) training increases FFA Ra, Rd, and Rox p whether measured at given absolute or relative exercise intensities, 3) whole body lipolysis (glycerol Ra) during exercise is not significantly impacted by training, and 4) training-induced increases in plasma FFA oxidation are the main contributor to elevated total FFA oxidation during exercise exertion after training.

    View details for DOI 10.1152/ajpendo.1998.275.5.E853

    View details for PubMedID 29585215

  • Training-induced alterations of carbohydrate metabolism in women: women respond differently from men JOURNAL OF APPLIED PHYSIOLOGY Friedlander, A. L., Casazza, G. A., Horning, M. A., Huie, M. J., Piacentini, M. F., Trimmer, J. K., Brooks, G. A. 1998; 85 (3): 1175-1186


    We examined the hypothesis that glucose flux was directly related to relative exercise intensity both before and after a 12-wk cycle ergometer training program [5 days/wk, 1-h duration, 75% peak O2 consumption (VO2 peak)] in healthy female subjects (n = 17; age 23.8 +/- 2.0 yr). Two pretraining trials (45 and 65% of VO2 peak) and two posttraining trials [same absolute workload (65% of old VO2 peak) and same relative workload (65% of new VO2 peak)] were performed on nine subjects by using a primed-continuous infusion of [1-13C]- and [6,6-2H]glucose. Eight additional subjects were studied by using [6, 6-2H]glucose. Subjects were studied postabsorption for 90 min of rest and 1 h of cycling exercise. After training, subjects increased VO2 peak by 25.2 +/- 2.4%. Pretraining, the intensity effect on glucose kinetics was evident between 45 and 65% of VO2 peak with rates of appearance (Ra: 4.52 +/- 0.25 vs. 5.53 +/- 0.33 mg . kg-1 . min-1), disappearance (Rd: 4.46 +/- 0.25 vs. 5.54 +/- 0.33 mg . kg-1 . min-1), and oxidation (Rox: 2.45 +/- 0.16 vs. 4.35 +/- 0.26 mg . kg-1 . min-1) of glucose being significantly greater (P

    View details for Web of Science ID 000075781500051

    View details for PubMedID 9729597